期刊
NANO RESEARCH
卷 14, 期 3, 页码 846-857出版社
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-020-3124-y
关键词
hyaluronate nanogel; self-targetability; intracellular drug codelivery; multimodal imaging; reversal of multidrug resistance
类别
资金
- National Key Research and Development Program of China [2016YFC1100701]
- National Natural Science Foundation of China [52022095, 51973216, 51873207]
- Science and Technology Development Program of Jilin Province [20200404182YY]
- Youth Innovation Promotion Association of Chinese Academy of Sciences [2019005]
- Brigham Research Institute
In this study, a self-targeting hyaluronate nanogel was developed for reversing drug resistance through synchronized pharmacokinetics, intratumoral distribution, and intracellular release of doxorubicin and cisplatin. This nanogel showed efficient drug delivery into drug-resistant breast cancer cells and enhanced antitumor activity, with potential for future clinical therapy of advanced cancers. Visualized synchronized drug delivery and imaging techniques facilitate the visualization of combination tumor chemotherapy.
Multidrug-resistance (MDR) featuring complicated and poorly defined mechanisms is a major obstacle to the success of cancer chemotherapy in the clinic. Compound nanoparticles comprising multiple cytostatics with different mechanisms of action are commonly developed to tackle the multifaceted nature of clinical MDR. However, the different pharmacokinetics and release profiles of various drugs result in inconsistent drug internalization and suboptimal drug synergy at the tumor sites. In the present study, a type of self-targeting hyaluronate (HA) nanogels ((CDDP)HANG/DOX) to reverse drug resistance through the synchronized pharmacokinetics, intratumoral distribution, and intracellular release of topoisomerase II inhibitor doxorubicin (DOX) and DNA-crosslinking agent cisplatin (CDDP) is developed. With prolonged circulation time and enhanced intratumoral accumulation in vivo, (CDDP)HANG/DOX shows efficient drug delivery into the drug-resistant MCF-7/ADR breast cancer cells and enhanced antitumor activity. Besides, fluorescence imaging of DOX combined with the micro-computed tomography (micro-CT) imaging of CDDP facilitates the visualization of this combination tumor chemotherapy. With visualizable synchronized drug delivery, the self-targeting in situ crosslinked nanoplatform may hold good potential in future clinical therapy of advanced cancers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据